Iron Deficiency and Erythropoiesis: New Diagnostic Approaches

Abstract

Iron deficiency anemia is one of the most common diseases worldwide. In the majority of cases, the presence of hypochromic microcytic anemia and biochemical evidence for depletion of body iron stores makes the diagnosis relatively straightforward. However, in several clinical conditions, classic biochemical indices such as serum iron, transferrin saturation, and ferritin may not be informative or may not change rapidly enough to reflect transient iron-deficient states (functional iron deficiency), such as the ones that develop during recombinant human erythropoietin (r-HuEPO) therapy. The identification and treatment of iron deficiency in settings such as r-HuEPO therapy, anemia of chronic disease, and iron deficiency of early childhood may be improved by the use of red cell and reticulocyte cellular indices, which reflect in almost real time the development of iron deficiency and the response to iron therapy. In the anemia of chronic disease, measurements of plasma cytokines and iron metabolism regulators such as hepcidin (when available) may be helpful in the characterization of the pathophysiologic basis of this condition. The ratio of serum transferrin receptor (sTfR) to serum ferritin (R/F ratio) has been shown to have excellent performance in estimating body iron stores, but it cannot be used widely because of the lack of standardization for sTfR assays. The combination of hematologic markers such as reticulocyte hemoglobin content, which decreases with iron deficiency, and R/F ratio may allow for a more precise classification of anemias.

Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications

“…It is important to distinguish between ACD and ACD/IDA to appropriately guide therapeutic regimens, especially in respect to iron repletion strategies. 7,27 We used a rat model of inflammation-associated chronic anemia to investigate the regulation of body iron homeostasis in ACD. We observed increased expression of the iron storage protein ferritin in the spleen but not in the liver, a finding in accordance with previous data demonstrating divergent ferroportin regulation by hepcidin in duodenum and liver.…”

“…As ferritin in the setting of inflammation does not accurately reflect iron stores, this has led others to use the ratio of sTfR/log ferritin, but this measurement has not gained acceptance and has several limitations. 7,9 Bone marrow aspiration stained with Prussian blue is considered the most reliable method of determining bone marrow iron stores, but this represents an invasive method. In contrast, serum hepcidin levels are an easy to obtain parameter and reflect the needs of iron for erythropoiesis in the setting of inflammation.…”

“…6 The functional iron deficiency present in patients with ACD can be complicated by true iron deficiency resulting from chronic blood loss. 7 Differentiation between ACD and ACD/iron deficiency anemia (IDA) is clinically important because iron supplementation is beneficial for ACD/IDA patients but may be deleterious for ACD patients, especially if these subjects have underlying infections or malignancies. 1 In clinical practice, however, differentiating between ACD and ACD/IDA is difficult, as both diseases present with decreased serum iron concentration and transferrin saturation.…”

Iron deficiency: A concise review

“…Definitive diagnosis requires laboratory tests [62]. A bone marrow smear containing no stainable iron is definitive.…”

Low Hemoglobin Density as a Measure of Iron Status

“…Iron status is the result of the balance between the rate of erythropoiesis and the amount of iron stored in the body. Various biochemical parameters have been used to assess iron status such as iron levels, transferrin, transferrin saturation and ferritin, and all of them may be influenced by acute phase response and are also expensive tests [1][2][3][4]. In our situation where patients cannot afford exhaustive tests to document iron deficiency we utilized the LHD values as a predictor of iron status based on the formula provided by Urrechaga [5].…”